The Utility of Interferon-Gamma Release Assays in TB-HIV co-infected Children

干扰素-γ释放测定在结核病-艾滋病毒合并感染儿童中的应用

• 批准号: 7338473
• 负责人: ANNA M MANDALAKAS
• 金额: $ 49.35万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7338473
• 关键词: Address; Adult; Africa South of the Sahara; Age; Age-Years; Agreement; Anti-Retroviral Agents; Antigens; Antitubercular Agents; Asses; Biological Assay; CD4 Positive T Lymphocytes; Calmette-Guerin Bacillus; Caring; Cause of Death; Cell Count; Cessation of life; Child; Child health care; Childhood; Clinical Management; Communities; Confounding Factors (Epidemiology); Contracts; Data; Data Collection; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Effectiveness; Enrollment; Exposure to; Genus Mycobacterium; Gold; HIV-1; Health Benefit; Household; Hypersensitivity skin testing; Immune; Immunization; Immunologic Markers; Infection; Institution; Interferon Type II; Knowledge; Lymphocyte Count; Measures; Methods; Morbidity - disease rate; Mycobacterium tuberculosis; Nutritional; Nutritional status; Performance; Population; Prevention; Preventive; Production; Public Health; Reporting; Research Design; Research Personnel; Risk; Score; Specificity; Standards of Weights and Measures; T-Lymphocyte; Testing; Time; Tube; Tuberculin; Tuberculosis; Vaccination; Viral Load result; aging nutrition; base; design; diagnostic accuracy; improved; indexing; interest; isoniazid; mortality; novel; prospective; response; tool

DESCRIPTION (provided by applicant): The principal objective of our project is to improve the health of children with Human Immunodeficiency Virus-1 (HIV) and Mycobacterium tuberculosis (M. tb) co-infection by accurately identifying those infected with M. tb. The study was designed to examine the utility and interpretation of Interferon-Gamma Release Assays (IGRA) in children with M.tb and HIV co-infection. There are limited data on the use of IGRA to detect M. tb infection in HIV-infected children/In a prospective community-based study in a setting highly endemic for tuberculosis (TB) and HIV, the following specific aims will be addressed in HIV-infected (N=300) and uninfected (N=500) children ¿5 years of age: 1) asses the agreement between the traditional tuberculin skin test (TST) and IGRAs, 2) assess the performance of the TST and IGRAs across a standard gradient of M. tb exposure, 3) measure the impact of potential interaction and confounding variables and 4) identify factors that modify children's response to TST and IGRA over time. We will utilize a community-based controlled TB household contact study design to describe both household and community M.tb exposure and infection through a standardized gradient of M.tb exposure (contact score). The standardized M. tb contact score will be a composite measure of the index case infectivity and the child's proximity and duration of contact with the TB index case. A focused set of standardized measures of age, nutrition and HIV-related immune status (CD4 T lymphocyte count) will be collected to fully assess their effect on the TST and IGRAs. Longitudinal analysis will also measure the influence of additional modifiers including time since exposure, anti-retroviral therapy, HIV viral load and isoniazid therapy. The proposed study involves primary data collection that wi-l address important gaps in our current knowledge regarding the utility and specific applicability of IGRAs for detection of M. tb infection in HIV-infected children. This includes identification of optimal cut-off values for interpretation of IGRAs in HIV-infected and -uninfected children in highly endemic settings. In HIV-infected children, those most vulnerable to TB-related morbidity and mortality IGRAs may assist in optimal clinical management through accurate and timely diagnosis and targeted preventive or curative therapy. Accurate diagnostic tools will also limit over diagnosis and treatment. Hence, IGRAs have great potential to improve TB control and decrease HIV-TB related disease and deaths in children. LAY DESCRIPTION: Novel Interferon Gamma Releases Assays have great potential to improve TB control and decrease HIV-TB related disease and deaths in children. However, it is imperative that the utility and interpretation of these tests be studied in HIV-infected children in settings with high burdens of TB and HIV.

描述（由适用提供）：我们项目的主要目的是通过准确识别患有M. TB的患者，改善人类免疫缺陷病毒-1（HIV）和结核分枝杆菌（M. TB）的儿童的健康状况。该研究旨在检查M. TB和HIV共同感染儿童中干扰素伽马释放分析（IGRA）的效用和解释。 There are limited data on the use of IGRA to detect M. tb infection in HIV-infected children/In a prospective community-based study in a setting highly endomic for tuberculosis (TB) and HIV, the following specific aims will be addressed in HIV-infected (N=300) and uninfected (N=500) children ¿ 5 years of age: 1) asses the agreement between the traditional tuberculin skin test (TST) and IGRAS，2）评估TST和IGRAS在M. TB暴露的标准梯度中的性能，3）测量潜在相互作用和混淆变量的影响； 4）确定因子随着时间而变化了儿童对TST和IGRA的反应的因素。我们将利用基于社区的控制结核病家庭接触研究设计来描述家庭和社区M.TB的暴露和感染，并通过标准化的M.TB暴露梯度（接触得分）来描述。标准化的M.TB接触评分将是指数病例感染的综合度量，以及与结核病指数案例的接近性和接触时间。将收集一组重点的标准化测量值，营养和与HIV相关的免疫状态（CD4 T淋巴细胞计数），以完全评估其对TST和IGRAS的影响。纵向分析还将衡量其他修饰符的影响，包括自暴露以来的时间，抗逆转录病毒疗法，HIV病毒载量和异烟肼治疗。拟议的研究涉及主要数据收集，即Wi-L解决了我们当前有关IGRAS在HIV感染儿童中检测M. TB感染的效用和特定应用的知识的重要差距。这包括识别在高度内在环境中对HIV感染和未感染的儿童解释IGRA的最佳临界值。在感染HIV的儿童中，最容易受到与TB相关的发病率和死亡率IGRAS的儿童可以通过准确，及时的诊断和靶向预防或治愈性治疗来帮助最佳临床管理。准确的诊断工具还将限制诊断和治疗。因此，IGRA具有改善结核病控制并减少HIV-TB相关疾病和儿童死亡的巨大潜力。外行描述：新型干扰素伽玛释放测定具有巨大的潜力，可以改善结核病控制并减少儿童相关的HIV-TB相关疾病和死亡。但是，必须在艾滋病毒感染的儿童中研究这些测试的效用和解释，以hiv感染的儿童具有高伯恩斯和艾滋病毒的伯恩斯。